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Tissue Engineering. Part B, Reviews Oct 2015For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment.... (Review)
Review
For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models. Due to limited data quantity and quality, current evidence levels are insufficient for further conclusions.
Topics: Animals; Dental Pulp; Humans; Regeneration; Stem Cell Transplantation
PubMed: 25919657
DOI: 10.1089/ten.TEB.2014.0675 -
BMJ Open Jun 2023Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Metformin is associated with osteoblastogenesis and osteoclastogenesis. This study aims to investigate the impacts of metformin therapy on bone mineral density (BMD) and bone turnover markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials.
METHODS
Searches were carried out in PubMed, EMBASE, Web of science, Cochrane library, ClinicalTrials.gov from database inception to 26 September 2022. Two review authors assessed trial eligibility in accordance with established inclusion criteria. The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB V.2.0). Data analysis was conducted with Stata Statistical Software V.16.0 and Review Manager Software V.5.3.
RESULTS
A total of 15 studies with 3394 participants were identified for the present meta-analysis. Our pooled results indicated that metformin had no statistically significant effects on BMD at lumbar spine (SMD=-0.05, 95% CI=0.19 to 0.09, p=0.47, participants=810; studies=7), at femoral (MD=-0.01 g/cm, 95% CI=-0.04 to 0.01 g/cm, p=0.25, participants=601; studies=3) and at hip (MD=0.01 g/cm, 95% CI=0.02 to 0.03 g/cm, p=0.56, participants=634; studies=4). Metformin did not lead to significant change in osteocalcin, osteoprotegerin and bone alkaline phosphatase. Metformin induced decreases in N-terminal propeptide of type I procollagen (MD=-6.09 µg/L, 95% CI=9.38 to -2.81 µg/L, p=0.0003, participants=2316; studies=7) and C-terminal telopeptide of type I collagen (MD=-55.80 ng/L, 95% CI=97.33 to -14.26 ng/L, p=0.008, participants=2325; studies=7).
CONCLUSION
This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the outcomes should be interpreted with caution due to several limitations.
Topics: Humans; Bone Density; Metformin; Lumbar Vertebrae; Bone Remodeling
PubMed: 37355276
DOI: 10.1136/bmjopen-2023-072904 -
Stem Cell Research & Therapy Jul 2021Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.
METHODS
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.
RESULTS
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).
CONCLUSION
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Topics: Animals; Bone Regeneration; Bone and Bones; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 34215342
DOI: 10.1186/s13287-021-02456-w -
Theranostics 2022In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes... (Review)
Review
In recent decades, extracellular vesicles (EVs), as bioactive cell-secreted nanoparticles which are involved in various physiological and pathological processes including cell proliferation, immune regulation, angiogenesis and tissue repair, have emerged as one of the most attractive nanotherapeutics for regenerative medicine. Herein we provide a systematic review of the latest progress of EVs for regenerative applications. Firstly, we will briefly introduce the biogenesis, function and isolation technology of EVs. Then, the underlying therapeutic mechanisms of the native unmodified EVs and engineering strategies of the modified EVs as regenerative entities will be discussed. Subsequently, the main focus will be placed on the tissue repair and regeneration applications of EVs on various organs including brain, heart, bone and cartilage, liver and kidney, as well as skin. More importantly, current clinical trials of EVs for regenerative medicine will also be briefly highlighted. Finally, the future challenges and insightful perspectives of the currently developed EV-based nanotherapeutics in biomedicine will be discussed. In short, the bioactive EV-based nanotherapeutics have opened new horizons for biologists, chemists, nanoscientists, pharmacists, as well as clinicians, making possible powerful tools and therapies for regenerative medicine.
Topics: Extracellular Vesicles; Kidney; Nanoparticles; Regenerative Medicine; Wound Healing
PubMed: 35836815
DOI: 10.7150/thno.72812 -
Tissue Engineering. Part C, Methods May 2023Bioactive glasses (BAGs) are surface-active ceramic materials that can be used in bone regeneration due to their known osteoconductive and osteoinductive properties....
Bioactive glasses (BAGs) are surface-active ceramic materials that can be used in bone regeneration due to their known osteoconductive and osteoinductive properties. This systematic review aimed to study the clinical and radiographic outcomes of using BAGs in periodontal regeneration. The selected studies were collected from PubMed and Web of Science databases, and included clinical studies investigating the use of BAGs on periodontal bone defect augmentation between January 2000 and February 2022. The identified studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 115 full-length peer-reviewed articles were identified. After excluding duplicate articles between the databases and applying the inclusion and exclusion criteria, 14 studies were selected. The Cochrane risk of bias tool for randomized trials was used to assess the selected studies. Five studies compared using BAGs with open flap debridement (OFD) without grafting materials. Two of the selected studies were performed to compare the use of BAGs with protein-rich fibrin, one of which also included an additional OFD group. Also, one study evaluated BAG with biphasic calcium phosphate and used a third OFD group. The remaining six studies compared BAG filler with hydroxyapatite, demineralized freeze-dried bone allograft, autogenous cortical bone graft, calcium sulfate β-hemihydrate, enamel matrix derivatives, and guided tissue regeneration. This systematic review showed that using BAG to treat periodontal bone defects has beneficial effects on periodontal tissue regeneration. OSF Registration No.: 10.17605/OSF.IO/Y8UCR.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Alveolar Bone Loss; Periodontium; Bone Transplantation; Bone Regeneration
PubMed: 37002888
DOI: 10.1089/ten.TEC.2023.0036 -
Archives of Orthopaedic and Trauma... Mar 2019Cartilage regeneration and restoration is a major topic in orthopedic research as cartilaginous degeneration and damage is associated with osteoarthritis and joint...
INTRODUCTION
Cartilage regeneration and restoration is a major topic in orthopedic research as cartilaginous degeneration and damage is associated with osteoarthritis and joint destruction. This systematic review aims to summarize current research strategies in cartilage regeneration research.
MATERIALS AND METHODS
A Pubmed search for models investigating single-site cartilage defects as well as chondrogenesis was conducted and articles were evaluated for content by title and abstract. Finally, only manuscripts were included, which report new models or approaches of cartilage regeneration.
RESULTS
The search resulted in 2217 studies, 200 of which were eligible for inclusion in this review. The identified manuscripts consisted of a large spectrum of research approaches spanning from cell culture to tissue engineering and transplantation as well as sophisticated computational modeling.
CONCLUSIONS
In the past three decades, knowledge about articular cartilage and its defects has multiplied in clinical and experimental settings and the respective body of research literature has grown significantly. However, current strategies for articular cartilage repair have not yet succeeded to replicate the structure and function of innate articular cartilage, which makes it even more important to understand the current strategies and their impact. Therefore, the purpose of this review was to globally summarize experimental strategies investigating cartilage regeneration in vitro as well as in vivo. This will allow for better referencing when designing new models or strategies and potentially improve research translation from bench to bedside.
Topics: Animals; Biomedical Research; Cartilage, Articular; Humans; Models, Biological; Regeneration; Tissue Engineering
PubMed: 30382366
DOI: 10.1007/s00402-018-3057-z -
Advances in Experimental Medicine and... 2021Periodontitis is an infectious inflammatory disease characterized by clinical attachment loss and tooth supporting tissue destruction. As exosomes demonstrated...
Periodontitis is an infectious inflammatory disease characterized by clinical attachment loss and tooth supporting tissue destruction. As exosomes demonstrated pro-regenerative ability, their use in periodontal treatment has been suggested. The aim of this systematic review is to gather and summarize the most recent data regarding exosomes to determine their potential impact in bone and periodontal regeneration. Electronic databases (Pubmed, Web of Science) were searched up to February 2020. Studies assessing the impact of exosomes administration in experimental bone and periodontal defects have been identified according to PRISMA guidelines. Among the 183 identified articles, 16 met the inclusion criteria and were included in this systematic review. Experimental bone defects were mainly surgically induced with a dental bur or distraction tools. All studies considered bone healing after exosomes administration as the primary outcome. Results showed that mesenchymal stem cells derived exosomes administration promoted bone healing and neovascularization. Nevertheless, a dose-effect relationship was observed. Exosomes administration appears to promote significantly the bone healing and periodontal regeneration. However, only a limited number of studies have been carried out so far and the optimized protocols in this context need to be evaluated.
Topics: Bone Regeneration; Bone and Bones; Exosomes; Guided Tissue Regeneration, Periodontal; Humans; Mesenchymal Stem Cells; Periodontitis
PubMed: 33159304
DOI: 10.1007/5584_2020_593 -
Wound Repair and Regeneration :... Jul 2022Skin and wound blotting are non-invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or... (Review)
Review
Skin and wound blotting are non-invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or broken cutaneous surface to detect biomarkers. However, there has been no comprehensive review of the evidence for the techniques used and data obtained to date. The primary aim of this study was to review the utilities of surface blotting for the diagnosis and prognosis of physiological, pre-disease, and pathological states. The secondary aim was to summarise the procedural steps. A systematic literature search was conducted on 9 July 2021 using Medline, Embase, and Google Scholar databases. Investigators used McMaster's Critical Review Form for Quantitative Studies to assess quality, then performed a narrative synthesis reporting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-five studies were reviewed. Eighteen studies were of good quality, and seven were of moderate quality. These studies conducted skin and wound blotting on 176 animals and 1546 humans. Studies reported physiological and pathological states for diagnosis and prediction of conditions, including skin tears, wound healing, biofilm detection, and skin barrier function. The four steps for blotting are surface preparation, blot preparation, application and removal of blot, and analysis. This review demonstrates that blotting can determine the skin and wound surface chemistry using a versatile and reproducible technique. However, future research is needed to validate the technique and skin biomarkers identified.
Topics: Animals; Prognosis; Skin; Soft Tissue Injuries; Wound Healing
PubMed: 35638724
DOI: 10.1111/wrr.13030 -
Stem Cell Research & Therapy May 2023Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals, with promising outcomes in new bone formation. Nevertheless, the clinical trial for bone regeneration using dental pulp stem cells is still in its infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models.
METHODOLOGY
This study was registered in PROSPERO (CRD2021274976), and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias were also carried out using the CAMARADES tool. Quantitative bone regeneration data of the experimental (scaffold + hDPSC/SHED) and the control (scaffold-only) groups were also extracted for meta-analysis.
RESULTS
Forty-nine papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold-only) (SMD: 1.863, 95% CI 1.121-2.605). However, the effect is almost entirely driven by the % new bone formation group (SMD: 3.929, 95% CI 2.612-5.246) while % BV/TV (SMD: 2.693, 95% CI - 0.001-5.388) shows a marginal effect. Dogs and hydroxyapatite-containing scaffolds have the highest capacity in % new bone formation in response to human DPSC/SHED. The funnel plot exhibits no apparent asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable.
CONCLUSION
This is the first synthesised evidence showing that human DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold irrespective of scaffold type and animal species used. So, dental pulp stem cells could be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies.
Topics: Adult; Animals; Dogs; Humans; Bone Regeneration; Cell Differentiation; Dental Pulp; Osteogenesis; Stem Cell Transplantation; Tissue Scaffolds
PubMed: 37189187
DOI: 10.1186/s13287-023-03357-w -
Journal of Orthopaedic Surgery and... Apr 2016Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and... (Review)
Review
Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.
Topics: Cartilage, Articular; Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regeneration; Tissue and Organ Harvesting
PubMed: 27072345
DOI: 10.1186/s13018-016-0378-x